One-pack preparation for disinfection, neutralization and cleaning of contact lenses and method of disinfection, neutralization and cleaning

ABSTRACT

The present invention provides a combined formulation for disinfecting, neutralizing and cleaning a soft contact lens and a method using the same easily, efficiently and safely. The formulation is a one-solution type of combined formulation for disinfecting, neutralizing and cleaning a soft contact lens, which includes a first formulation that contains an iodine-based disinfectant and a proteolytic enzyme and a second formulation that contains a reducing and a foaming agent treated with a delayed release coating, and which contains a nonionic surfactant in at least one of the first and second formulations. A stained soft contact lens can be disinfected, neutralized and cleaned easily by holding it in an aqueous solution colored yellow or brown by iodine molecules and removing it from the aqueous solution after the solution becomes almost colorless.

FIELD OF THE INVENTION

This invention relates to a one-solution type of combined formulationfor disinfecting, neutralizing and cleaning contact lenses and a methodof caring for contact lenses using the same. More specifically, itrelates to a one-solution type of combinated formulation suitable fordisinfecting, neutralizing and cleaning soiled contact lenses quicklyand simply, and a method for caring for a contact lenses using the same.

PRIOR ART

Methods that have been currently used for disinfecting soft contactlenses are roughly divided into disinfection by boiling and disinfectionby chemicals. Although disinfection by boiling is substantiallyeffective for the disinfection of all kinds of microorganisms such asbacteria, viruses and molds, it may cause a lens to become whiteturbidity due to the denaturation and coagulation of protein or othersubstances adhering to a soft contact lens by heat or the deformationand discoloration of a lens by long-term repeated heating. This methodhas such inconvenience that it cannot be used without a power source.

A large number of methods for disinfection by chemicals have been alsoknown, and some of 3% hydrogen peroxide and biguanide-based antisepticsolutions have a low sterilizing effect according to types ofmicroorganisms. When misused, they act as an excessively strong irritantto the cornea epithelium and conjunctiva and may cause a disorder of thecornea.

Of various halogen-based disinfectants, iodine-based disinfectants areexcellent chemical disinfectants in terms of sterilizing effect andsafety to eyes. Examples of disinfection using these iodine-baseddisinfectants are described in the specification of UK Patent No.1,604,020, the specification of U.S. Pat. No. 4,312,833, Contacto, pp.33 to 37 (1975), the Bulletin No. 23 of the Japan Contact Lens Society,pp. 150 to 154 (1981) and the Bulletin No. 20 of the Japan Contact LensSociety, pp. 96 to 101 (1978). However, in these methods, the removaland neutralization of the residual disinfectant after disinfection usingan iodine-based disinfectant are carried out by the self-sublimation ofiodine or using a weak reducer. Therefore, the removal of active iodinetakes a long time and the neutralization may be incomplete. As a result,a soft contact lens may be changed color as the iodine agent is adsorbedto the matrix of the lens and may be deformed or deteriorated by thereaction between iodine and the lens material.

Further, though the iodine formulation is relatively safe to eyes, whenit is adsorbed and accumulated in a lens without being completelyneutralized, an iodine-based chemical is gradually released while thelens is worn and may inflame the eyes of an allergic person or cause adisorder of the cornea, as described in Annals Ophthalmology, pp. 361 to364 (1981). WO 96/00590 and WO 96/00591 disclose a method fordisinfecting contact lens and subsequent reduction, wherein the lens arecontacted with a solution combinated with a reducing solution and anexcess amount of iodine formulation than the required amount foroxidizing a contained reducer, and further a reducer is added to reducethe residual iodine formulation. In addition, of cares of a soft contactlens, it is important to remove protein or lipid adhering to a lens, anda cleaning agent is required for this purpose. However, there has notbeen yet known a one-solution type of combinated formulation comprisingan iodine disinfectant, neutralizer, proteolytic enzyme and surfactant.

SUMMARY OF THE INVENTION

It is an object of the present invention to provide a one-solution typeof combinated formulation for carrying out disinfection, neutralizationand cleaning in one solution.

It is another object of the present invention to provide a one-solutiontype of combinated formulation suitable for disinfecting, neutralizingand cleaning a soiled contact lens quickly and easily.

It is still another object of the present invention to provide aone-solution type of combinated formulation for disinfecting,neutralizing and cleaning a soft contact lens easily, which comprisesnot only of an iodine disinfectant exhibiting a strong sterilizingeffect but also relatively high safety to improve the defect of aformulation using a neutralization method of the prior art bycombinating two other formulations.

It is still another object of the present invention to provide a methodfor cleaning a soiled contact lens quickly and easily using theone-solution type of combinated formulation of the present invention.

Other objects and advantages of the present invention will becomeapparent from the following description.

According to the present invention, firstly, the above objects andadvantages of the present invention can be attained by a one-solutiontype of combinated formulation for disinfecting, neutralizing andcleaning a contact lens, which comprises (A) the first formulationcontaining an iodine-based disinfectant and a proteolytic enzyme and (B)the second formulation containing a reducer and a foaming agent andhaving a delayed release coating, and containing a nonionic surfactantin at least one of the first and second formulations.

The one-solution type of combinated formulation of the present inventioncomprises the first formulation (A) and the second formulation (B) atleast one of which contains a nonionic surfactant.

The first formulation contains an iodine-based disinfectant and aproteolytic enzyme, and a nonionic surfactant as the case may be.

The iodine-based disinfectant advantageously used in the presentinvention is conventionally well-known as povidone iodine or polyvinlyalcohol iodine wherein iodine molecules (I₂) are included inmacromolecule such as polyvinyl pyrrolidone (PVP) or polyvinyl alcohol(PVA). These macromolecule-coupled iodine agents are extremely excellentdisinfectants which (1) are water-soluble, (2) stabilize subliming andunstable iodine molecules in a solid state, and (3) reduce toxicity, ascompared with free iodine agents, and which have strong bactericidalaction equal to that of free iodine agents. Namely, the disinfectantshave a wide range of antibacterial spectra against bacteria, antibioticresistant germs, molds, viruses and the like.

The proteolytic enzyme advantageously used in the present invention mustretain sufficient cleaning power for a lens soiled with protein in thepresence of the iodine disinfectant which is a strong oxidant. Since asulfur group, that is, particularly sulfur atoms such as a thiol groupor dithio group, are readily oxidized by an iodine compound, theactivity of enzymes having a large number of these sulfur groups, suchas papain, bromelain, ficin, pancreatin and cathepsin is greatly reducedby the presence of the iodine disinfectants. Therefore, they cannot berecommended as a preferred enzyme cleaning agent in the presentinvention.

Experiments have been conducted on stability using various enzymes underthe presence of the iodine formulation. As a result, it has been foundthat proteolytic enzymes produced by bacillus bacteria and enzymesderived from animal pancreases are relatively stable.

Proteolytic enzymes available on the market include Bioprase,Biotamilase (of Nagase Biochemicals Ltd.), Protease N “Amano” (of AmanoPharmaceutical Co., Ltd.), Subtilisin A, Alcarase, Esperase, Trypsin,Chymotrypsin (of Novo Nordisk Bioindustry Ltd.) and the like. A suitableone is selected out of these.

The first formulation contains an iodine-based disinfectant preferablyin an amount of 0.01 to 50 wt %, more preferably 0.1 to 15 wt %, basedon the first formulation. When the first formulation is dissolved in anaqueous solution as the combinated formulation of the present invention,the iodine-based disinfectant is contained in the aqueous solutionpreferably in an amount of 1 to 5,000 ppm, more preferably 10 to 1,500ppm in terms of the concentration of effective iodine. If theconcentration is less than 1 ppm, the disinfecting power of thedisinfectant will lower. On the other hand, if the concentration is morethan 5,000 ppm, the disinfectant will have a prolonged neutralizationtime and affect a lens, thereby making it difficult to handle.

And the first formulation contains a proteolytic enzyme preferably in anamount of 0.01 to 50 wt %, more preferably 0.1 to 20 wt % based on thefirst formulation. When the first formulation is dissolved in an aqueoussolution as the combinated formulation of the present invention, theconcentration of the proteolytic enzyme contained in the aqueoussolution, which is suitably determined according to its cleaning effectand enzyme activity, is preferably 0.0001 to 0.5 wt %.

Preferred examples of the nonionic surfactant which the firstformulation may contain, include Poloxamer (polyoxyethylene,polyoxypropylene block polymer), Poloxamine (polyoxyethylene,polyoxypropylene block polymer of ethylene diamine), Polysorbate 80(polyoxyethylene 20 sorbitan monooleate), Polyoxyl 40 (polyethyleneglycol monostearate) Stearate and Polyoxyethylene Hydrogenated CastorOil 60.

The nonionic surfactant is contained in the first formulation preferablyin an amount of 0.01 to 50 wt %, more preferably 0.1 to 20 wt% based onthe first formulation. When the combinated formulation of the presentinvention is dissolved in an aqueous solution, the nonionic surfactantis contained in the aqueous solution preferably in an amount of 0.0001to 0.5 wt %, more preferably 0.001 to 0.2 wt %.

Meanwhile, the second formulation contains a sulfur-containing reducerand a foaming agent, and a nonionic surfactant as required, and has adelayed release coating.

As the reducer, may be used the known powerful reducers for iodine andhalogenating agents. Sodium sulfite, sodium hydrogen sulfite, sodiumthiosulfate, ascorbic acid and sodium ascorbate are particularlypreferred because they effectively reduce iodine molecules remaining ina soft contact lens after disinfection.

The reducer is contained preferably in an amount of 0.01 to 50 wt %,more preferably 0.1 to 20 wt % based on the second formulation. When thesecond formulation is dissolved in purified water as the combinatedformulation of the present invention, the reducer eventually reacts withan iodine-based disinfectant for reduction.

In addition the foaming agent is preferably sodium bicarbonate or sodiumcarbonate, for example.

The foaming agent is contained preferably in an amount of 1 to 80 wt %,more preferably 10 to 60 wt % based on the second formulation.

Further, examples of the nonionic surfactant which the secondformulation may contain, are the same as those listed for the firstformulation.

The second formulation can also contain a nonionic surfactant in thesame amount as that of the first formulation.

The second formulation has a delayed release coating. The reason forthis is as follows.

The aqueous solution of iodine molecules is colored dark brown to yellowaccording to its concentration, and iodine is easily adhered to anorganic compound as is evident from the fact that it is used as acolorant for thin-layer chromatography for silica gel or alumina. Sincea soft contact lens to be disinfected is made from a polymer of anorganic compound such as a methacrylic acid derivative, acrylamidederivative or N-vinyl pyrrolidone, iodine molecules are easily adheredto the matrix of a lens at the time of disinfection, whereby the lens iscolored yellow or brown. When this state lasts long, it may exert suchinfluences as the denaturation and deterioration of the lens material.When the iodine molecules are reduced by the reducer after disinfection,they are converted into iodo anion (I⁻), which is colorless and safe andhas almost no adsorption power to the lens matrix.

Therefore, it is necessary to reduce the residual excess iodinemolecules by the reducer as soon as disinfection is effectively carriedout with iodine. For this purpose, the second formulation has a delayedrelease coating to release the reducer or the like after the contactlens is disinfected by the first formulation.

In other words, merely by holding a soiled lens in an aqueous solutioncontaining the first formulation and the second formulation, the contactlens is first disinfected and cleaned by the first formulation,continuous dissolution of the delayed released coating of the secondformulation is completed when the disinfection is almost completed, andfinally the residual excess iodine molecules are reduced (neutralized)by the reducer contained in the second formulation. The foaming agentcontained in the second formulation assists this reduction reactioneffectively and smoothly.

Preferred examples of the delayed release coating used in the presentinvention include chemically modified celluloses and gelatins. Of these,hydroxypropylcellulose (HPC), hydroxypropylmethylcellulose (HPMC) andhydroxyethylcellulose (HEC) are more preferred.

The delayed release coating is preferably designed to start foaming in 1to 10 minutes.

In other words, as for the disinfection and cleaning of a contact lensby the first formulation, that is, disinfection by an iodine-baseddisinfectant and cleaning by a proteolytic enzyme, since thedisinfection time is suitably 1 to 10 minutes for carrying out enoughdisinfection due to ensuring enough cleaning by suppressing thedeactivation of the proteolytic enzyme, it is desirable that theeffective components of the second formulation are set to be activeafter disinfection and cleaning by the first formulation.

Therefore, the first formulation is preferably in a powdery or granularform and the second formulation is in the form of a tablet or capsule,or the second formulation forms a center portion and the firstformulation covers the center portion as an outer layer (such as anucleated tablet), or the first and second formulations are in such aform that they are placed side by side. In the latter two forms, it ispossible to prevent an involuntary failure to add one of theformulations into a solution.

Therefore, according to the present invention, secondly, there is alsoprovided a method for disinfecting, neutralizing and cleaning a contactlens, which comprises the steps of holding a soiled contact lens in ayellow or brown aqueous solution containing the one-solution type ofcombinated formulation of the present invention and removing the contactlens from the aqueous solution after the aqueous solution becomes almostcolorless.

The aqueous solution containing the one-solution type of combinatedformulation can contain a isotonicity, buffer and chelating agent. Theaqueous solution is preferably prepared, for example, by dissolving atleast one isotonicity selected from the group consisting of sodiumchloride and potassium chloride, at least one buffer selected from thegroup consisting of phosphates, boric acid and borates, and a chelatingagent selected from the group consisting of ethylenediamine disodiumtetraacetate (EDTA·2Na) and ethylenediamine dipotassium tetraacetate inpurified water. As this aqueous solution can be used as a lens rinsingsolution after used to disinfect and clean a soft contact lens, it isdesired that the isotonicity and pH of the solution are equal to thoseof human tears.

The method for disinfecting, neutralizing and cleaning of the presentinvention can be applied to all of known hydrous soft contact lenses.Stated more specifically, a lens is held in a basket fixed to the cap ofa capped vial after the vial is filled with an aqueous solution, thefirst and second formulations are added into the aqueous solution at thesame time, the cap having the lens fixed in the basket is closed, andthen the vial is shaken several times and allowed to stand. First ofall, the disinfectant and cleaning agent of the first formulationdissolve in the aqueous solution and start the disinfection ofmicroorganisms adhering to the lens and the cleaning of protein adheringto the same. Thereafter, the foaming of the neutralizer of the secondformulation starts after 1 to 10 minutes, and it can be observedvisually that the solution and the soft contact lens colored yellow orbrown and the soft contact lens are gradually discolored and becomecolorless eventually. Cleaning is continued during this procedure andcompletes in 1 to 600 minutes after the start of cleaning. The lensdisinfected, neutralized and cleaned is rinsed using the aforementionedrinsing solution and put on eyes.

EXAMPLES

The following examples are given to further illustrate the presentinvention. However, it should be understood that the present inventionis not limited by these examples.

Example 1

Components mg/formulation The First Formulation (powder) Povidone iodine3 (iodine-based disinfectant) Subtilisin A (proteolytic enzyme) 6Lactose (excipient) 91  The Second Formulation (tablet) Sodium hydrogensulfite 3 Poloxamer (nonionic surfactant) 5 Sodium carbonate 30 (foaming agent, pH adjustor) Citric acid (pH adjustor) 10  Lactose(excipient) 12  HEC (coating) 5

After a tablet was formed, it was coated with HEC.

Aqueous Solution (liquid) Components mg/ml Sodium chloride (isotonicity)8 EDTA.2Na (chelating agent) 1 Boric acid (buffer) 5 Borax (buffer) 1Purified water (solvent) proper quantity

The above first formulation (powder) and the above second formulation(tablet) were packaged in an aluminum three-sealed-side package toprepare a one-solution type of combined formulation. The aqueoussolution (liquid) was charged into a PE bottle.

Example 2

Components mg/formulation The First Formulation (granule) Povidoneiodine 3 (iodine-based disinfectant) Trypsin (proteolytic enzyme) 3Polyoxyl 40 Stearate 5 (nonionic surfactant) Lactose (excipient) 87  TheSecond Formulation (tablet) Sodium sulfite (reducer) 3 Sodium carbonate30  (foaming agent, pH adjustor) Citric acid (pH adjustor) 10  Lactose(excipient) 12  HPMC (coating) 5

After a tablet was formed, it was coated with HPMC.

Aqueous Solution (liquid) Components mg/ml Sodium chloride (isotonicity)7 EDTA.2Na (chelating agent) 1 Monopotassium phosphate (buffer) 1Disodium phosphate (buffer)   1.5 Purified water (solvent) properquantity

The above first formulation (granule) and the above second formulation(tablet) were packaged in an aluminum three-sealed-side package toprepare a one-solution type of combined formulation. The aqueoussolution (liquid) was charged into a PE bottle.

Example 3

Components mg/formulation The First Formulation (powder) Povidone iodine3 (iodine-based disinfectant) Trypsin (proteolytic enzyme) 1Chymotrypsin (proteolytic enzyme) 1 Poloxamer (nonionic surfactant) 5Lactose (excipient) 90  The Second Formulation (capsule) Sodiumthiosulfate (reducer) 2 Sodium bicarbonate 30  (foaming agent, pHadjustor) Citric acid (pH adjustor) 5 Lactose (excipient) 13  Gelatin(encapsulating agent) 5

After granules were prepared, they were charged into a gelatin capsule.

Aqueous Solution (liquid) Components mg/ml Sodium chloride (isotonicity)6 EDTA.2Na (chelating agent) 1 Boric acid (buffer) 6 Borax (buffer)  1.5 Purified water (solvent) proper quantity

The above first formulation (powder) and the above second formulation(capsule) were packaged in an aluminum three-sealed-side package toprepare a one-solution type of combined formulation. The aqueoussolution (liquid) was charged into a PE bottle.

Comparative Example 1

Components The First Formulation (powder) mg/formulation Povidone iodine3 (iodine-based disinfectant) Papain (proteolytic enzyme) 7 Lactose(excipient) 90  The Second Formulation (tablet) Sodium hydrogen sulfite(reducer) 3 Poloxamer (nonionic surfactant) 5 Sodium carbonate 30 (foaming agent, pH adjustor) Citric acid (pH adjustor) 10  Lactose(excipient) 12  Aqueous Solution (liquid) mg/ml Sodium chloride(isotonicity) 8 EDTA.2Na (chelating agent) 1 Boric acid (buffer) 5 Borax(buffer) 1 Purified water (solvent) proper quantity

The above first formulation (powder) and the above second formulation(tablet) were packaged in a aluminum three-sealed-side-package toprepare a one-solution type of combined formulation. The aqueoussolution (liquid) was charged into a PE bottle.

Example 4

The disinfection effects of the formulations prepared in Examples 1 to 3and Comparative Example 1 were examined. The first and secondformulations of each of Examples 1 to 3 and Comparative Example 1 wereadded at the same time to 10 ml of a solution prepared by addingmicroorganisms to each of the above aqueous solutions at a density of10⁶ cfu/ml. After the second formulation was completely dissolved, 1 mlof the solution each was taken to a Petri dish to check the number ofviable microorganisms. The results are shown in Table 1.

TABLE 1 Disinfection Effect Test (cfu/ml) Inoculated ComparativeMicroorganisms Example 1 Example 2 Example 3 Example 1 S. aureus 0 0 010⁶ P. aeruginosa 0 0 0 10⁶ E. coli 0 0 0 10⁶ S. marcescens 0 0 0 10⁶ C.albicans 0 0 0 10⁶ A. niger 0 0 0 10⁶

As is evident from Table 1, the disinfection effects of the formulationsof Examples 1 to 3 are clearly observed. Since the second formulation ofComparative Example 1 did not have a delayed release coating, thedisinfectant was immediately neutralized and the disinfection effect wasnot obtained at all.

Example 5

The cleaning effects of the formulations prepared in Examples 1 to 3were examined. A HEMA lens was immersed in a 0.1% lysozyme solution andheated at 80° C. for 30 minutes to adhere thermally denatured lysozymeto the lens. This lens was scrubbed with a saline solution to obtain anartificially soiled lens. The artificially soiled lens was directlyplaced in each vial without fixation, 8 ml of each of the aqueoussolutions prepared in Examples 1 to 3 was added to the vial, the firstformulation and the second formulation were added into the vial, thelens was taken out from the vial after 4 hours, and the transmittancesof the lens at 500 nm before and after staining and after treatment weremeasured. The removal rate of lysozyme was calculated from the followingequation to check a cleaning effect.

Removal Rate of Lysozyme (%)=(T2−T1)/(T0−T1)×100

T0: transmittance of lens before staining

T1: transmittance of lens after staining

T2: transmittance of lens after treatment

The results are shown in Table 2.

TABLE 2 Cleaning Effect (removal rate of soiled, %) Comparative Numberof Tests Example 1 Example 2 Example 3 Example 1 1 78.2 88.6 90.1 10.5 2 85.5 82.8 89.9 5.2 3 88.2 91.5 85.0 8.8 Average Value 84.0 87.5 88.38.2

As is evident from Table 2, the cleaning effects of the formulations ofExamples 1 to 3 were observed. In Comparative Example 1, the proteolyticenzyme became deactivated and the cleaning effect was hardly observed.

Example 6

The safety of each formulation was tested using the eyes of houserabbits. Six HEMA lenses were fixed in respective vials and 8 ml of theaqueous solution prepared in Example 1 was added to each of the vials.Thereafter, the first formulation and the second formulation were addedinto each of the vials in the same manner and allowed to stand to carryout disinfection, neutralization and cleaning in one solution. After 4hours, each lens was taken out, rinsed with the above aqueous solutionand put on six eyes of house rabbits for 8 hours on the first day. Onand after the second day, the same operation as described above wasrepeated for 5 days, and the eye irritancy of this system was evaluatedevery day. The evaluation was based on the observed score according tothe criteria of Dratze (J. H. Draize, Association of Food and DrugOfficials of the United States, Topeka, Kansas, pp.46, 1959) and on thecorneal staining density with fluorescein immediately after removal ofthe lens from tested eyes on each day.

The Dratze score results of the safety test using the eyes of the houserabbits are shown in Table 3.

TABLE 3 Eye Number 1 2 3 4 5 6 Date of Wearing Site 12345 12345 1234512345 12345 12345 Cornea (A) Opacity - 00000 00000 00000 00000 0000000000 Degress of Density (B) Area of 00000 00000 00000 00000 00000 00000Opacity Iris (A) Values 00000 00000 00000 00000 00000 00000 Conjunctiva(A) Redness 10111 11100 11111 11111 10110 10011 (B) Chemosis 00000 0000000000 00000 00000 00000 (C) Discharge 10000 10000 10000 11001 0000010000 Total Points 40222 42200 42222 44224 20220 40022 Staining of Allthe test eyes were not stained. Cornea

Only slight redness and discharge were observed sporadically in contactlenses treated with the formulation prepared in Example 1 while theywere worn, and no symptom suggesting corneal toxicity was obtained fromthe fluorescein staining test.

No lesion was observed on the formulations prepared in Examples 2 and 3as well as the above result.

The criteria of the Draize method are shown in Table 4.

TABLE 4 Evaluated Site Degree of Reaction Point Cornea (A) Opacity -Degree of Density 0 • Transparent, no opacity • Scattered or diffusearea, details of iris 1 clearly visible • Easily discernible translucentareas, details of 2 iris slightly obscured • Opalesent areas no detailsof iris visible, size of 3 pupil barely discerible • Opaque, irisinvisible 4 (B) Area of Cornea • 0˜1/4 1 • 1/4˜1/2 2 • 1/2˜3/4 3 •3/4˜4/4 4 Iris (A) Values • Normal 0 • Folds above normal, congestion,swelling 1 circumcorneal injection (any or all of these or combinationof any thereof), iris still reacting to light sluggish reaction ispositive) • No reaction to light, hemorrhage, gross 2 destruction (anyor all of these.) Con- (A) Redness of Palpebral and Bulbar Conjunctivajunctiva • Vessels normal 0 • Vessels definitely injected above normal 1• More diffuse, deeper crimson red, individual 2 vessels not clearlydiscernible • Diffuse beefly red 3 (B) Chemosis • No swelling 0 • Anyswelling above normal (includes 1 nictitating membrane) • Obviousswelling with partial eversion of lids 2 • Swelling with lids about halfclosed 3 • Swelling with lids about half closed to 4 completely closed(C) Discharge • No discharge 0 • Any amount different from normal (doesnot 1 include amount observed in inner thus of normal ) • Discharge withmoistening of the lids and hairs 2 just adjacent to lids • Dischargewith moistening of the lids and hairs, 3 and considerable area aroundthe eye

Evaluation points were determined by the symptoms and observations ofthe eye tissues and the safety of the formulation was evaluated by thetotal of these. Calculation of The Total of The evaluation points:

Total Points=[cornea:A×B×5+iris:A×5+conjunctiva:(A+B+C)×2]

Evaluation:

0 to 5 points: no irritating

5 to 15 points: slightly irritating

15 to 30 points: irritating

30 to 60 pints: moderately irritating

60 to 80 points: moderately to strongly irritating

80 to 110 points: strongly irritating

According to the present invention, by simultaneously adding aformulation that contains an iodine-based disinfectant and a proteolyticenzyme and a formulation that contains a neutralizer treated with adelayed release coating and a surfactant into a vial that contains asoft contact lens and an aqueous solution, after bacteria adhering tothe lens can be disinfected completely in a short period of time, thecompletion of neutralization can be confirmed visually because theaqueous solution and the lens colored by iodine became colorless by aneutralizer, and protein and lipid adhering to the lens can be cleanedautomatically. Therefore, a series of lens cares, that is, disinfection,neutralization and cleaning can be carried out easily, efficiently andsafely.

What is claimed is:
 1. A one-solution type of combined formulation fordisinfecting, neutralizing and cleaning a contact lens, which comprises:(A) a first formulation containing an iodine-based disinfectant as asole disinfectant and a proteolytic enzyme, wherein said iodine-baseddisinfectant is a member selected from the group consisting of povidoneiodine and polyvinyl alcohol iodine, and (B) a second formulationcontaining a reducer and a foaming agent and having a delayed releasecoating, said reducer reduces iodine molecules remaining in a softcontact lens after disinfection and is a member selected from the groupconsisting of sodium hydrogen sulfite, sodium sulfite, sodium thiosulfate, ascorbic acid and sodium ascorbate, and at least one of thefirst and the second formulations containing a nonionic surfactant. 2.The one-solution type of combined formulation of claim 1, wherein theiodine-based disinfectant is contained in an amount of 0.01 to 50 wt %based on the first formulation.
 3. The one-solution type of combinedformulation of claim 1, wherein the proteolytic enzyme of the firstformulation is selected from the group consisting of enzymes derivedfrom bacillus bacteria and enzymes derived from animal pancreases. 4.The one-solution type of combined formulation of claim 1, wherein theproteolytic enzyme is contained in an amount of 0.01 to 50 wt % based onthe first formulation.
 5. The one-solution type of combined formulationof claim 1, wherein the nonionic surfactant is selected from the groupconsisting of polyoxyethylene-polyoxypropylene block polymer,polyoxyethylene-polyoxypropylene block polymer of ethylene di-amine,polyoxyethylene 20 sorbitan monooleate, polyethylene glycol monostearateand polyoxyethylene hydrogenated castor oil
 60. 6. The one-solution typeof combined formulation of claim 1, wherein the iodine-baseddisinfectant of the first formulation is povidone iodine or polyvinylalcohol iodine, the proteolytic enzyme is selected from enzymes derivedfrom bacillus bacteria and enzymes derived from animal pancreases, andthe nonionic surfactant of the first or the second formulation isselected from the group consisting of polyoxyethylene-polyoxypropyleneblock copolymer, polyoxyethylene-polyoxypropylene block copolymer ofethylene di-amine, polyoxyethylene 20 sorbitan monooleate, polyethyleneglycol monostearate and polyoxyethylene hydrogenated castor oil
 60. 7.The one-solution type of combined formulation of claim 1, wherein thereducer is contained in an amount of 0.01 to 50 wt % based on the secondformulation.
 8. The one-solution type of combined formulation of claim1, wherein the foaming agent of the second formulation is selected fromthe group consisting of sodium bicarbonate and sodium carbonate.
 9. Theone-solution type of combined formulation of claim 1, wherein thefoaming agent is contained in an amount of 1 to 80 wt% based on thesecond formulation.
 10. The one-solution type of combined formulation ofclaim 1, wherein the delayed release coating of the second formulationis made from a compound selected from the group consisting ofhydroxyethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methylcellulose and gelatin.
 11. The one-solution type of combined formulationof claim 1, wherein the delayed release coating of the secondformulation delays the release of the foaming agent by at least 1 to 10minutes after the second formulation is injected into an aqueoussolution.
 12. The one-solution type of combined formulation of claim 1,wherein the reducer of the second formulation is selected from the groupconsisting of sodium hydrogen sulfite, sodium sulfite, sodiumthiosulfate, ascorbic acid and sodium ascorbate, the foaming agent isselected from the group consisting of sodium bicarbonate and sodiumcarbonate, and the delayed release coating is made from a compoundselected from the group consisting of hydroxyethyl cellulose,hydroxypropyl cellulose, hydroxypropyl methyl cellulose and gelatin. 13.The one-solution type of combined formulation of claim 1, wherein theweight ratio of the first formulation to the second formulation is inthe range of 10/90 to 90/10.
 14. The one-solution type of combinedformulation of claim 1, wherein the first formulation is in a powdery orgranular form and the second formulation is in a tablet or capsule form.15. The one-solution type of combined formulation of claim 1, whereinthe second formulation forms a center portion and the first formulationforms an outer layer covering the center portion.
 16. The one-solutiontype of combined formulation of claim 1, wherein the proteolytic enzymesof the first formulation is selected from the group consisting ofenzymes derived from bacillus bacteria and enzymes derived from animalpancreases, the foaming agent of the second formulation is selected fromthe group consisting of sodium bicarbonate and sodium carbonate, thedelayed release coating of the second formulation is made from acompound selected from the group consisting of hydroxypropyl cellulose,hydroxypropyl methyl cellulose and gelatin, and the nonionic surfactantof each of the first and the second formulation is selected from thegroup consisting of polyoxyethylene-polyoxypropylene block polymer,polyoxyethylene-polyoxypropylene block polymer of ethylene diamine,polyoxyethylene 20 sorbitan monooleate, polyethylene glycol,monostearate and polyoxyethylene hydrogenated castor oil
 60. 17. Amethod of disinfecting, neutralizing and cleaning a contact lens, whichcomprises the steps of: holding a soiled contact lens in a yellow orbrown aqueous solution in which the first formulation (A) of theone-solution type of combined formulation of claim 1 is dissolved andremoving the contact lens from the aqueous solution after the secondformulation is dissolved in the aqueous solution and the aqueoussolution becomes almost colorless.
 18. The method of claim 17, whereinwhen the first and second formulations are added into the aqueoussolution at the same time, the first formulation dissolves first toclean and disinfect the lens, and thereafter, the reducer and foamingagent of the second formulation substantially start to dissolve toneutralize the iodine-based disinfectant.
 19. The method of claim 17,wherein the contact lens is removed from the aqueous solution 1 to 600minutes after the aqueous solution becomes almost colorless byneutralization.
 20. The method of claim 17, wherein the aqueous solutionfurther contains at least one isotonicity selected from the groupconsisting of sodium chloride and potassium chloride.
 21. The method ofclaim 17, wherein the aqueous solution further contains at least onebuffer selected from the group consisting of phosphates, boric acid andborates.
 22. The method of claim 17, wherein the aqueous solutionfurther contains at least one chelating agent selected from the groupconsisting of ethylenediamine disodium tetraacetate and ethylenediaminedipotassium tetraacetate.
 23. The method of claim 17, wherein theaqueous solution contains at least one isotonicity selected from thegroup consisting of sodium chloride and potassium chloride, at least onebuffer selected from the group consisting of phosphates, boric acid andborates and at least one chelating agent selected from the groupconsisting of ethylenediamine disodium tetraacetate and ethylenediaminedipotassium tetraacetate.
 24. A one-solution type of combinedformulation for disinfecting, neutralizing and cleaning a soft contactlens, which comprises: (A) a first formulation consisting essentially ofan iodine-based disinfectant and a proteolytic enzyme, and (B) a secondformulation consisting essentially of a reducer and a foaming agent andhaving a delayed release coating, at least one of the first and thesecond formulations contains a nonionic surfactant, wherein theiodine-based disinfectant of the first formulation is a member selectedfrom the group consisting of povidone iodine and polyvinyl alcoholiodine and the proteolytic enzyme is a member selected from the groupconsisting of enzymes derived from bacillus bacteria and enzymes derivedfrom animal pancreases, and wherein the nonionic surfactant is selectedfrom the group consisting of polyoxyethylene-polyoxypropylene blockpolymer, polyoxyethylene-polyoxypropylene block polymer of ethylenedi-amine, polyoxyethylene 20 sorbitan monooleate, polyethylene glycolmonostearate and polyoxyethylene hydrogenated castor oil 60.